The effect of prevention of reactive hyperemia, which invariably follows release of arterial occlusion in areas of the brain subjected to ischemia of intensity below threshold levels, was evaluated with regard to opening of the blood-brain barrier (BBB) associated with extravasation of serum proteins, and to development of ischemic brain edema. The reactive hyperemia was abolished by hypovolemic withdrawal of the blood at the time of recirculation. Such animals showed no opening of the BBB to proteins and significantly reduced edema, when tested at 3 hours following recirculation, in comparison to edema in normovolemic animals subjected to similar intensity of one hour ischemia. These studies demonstrate further the significance of serum protein extravasation in the development of brain edema.